Chronic oral administration of adipoRon reverses cognitive impairments and ameliorates neuropathology in an Alzheimer's disease mouse model.

Molecular Psychiatry
Roy Chun-Laam NgKoon-Ho Chan

Abstract

Circulating adiponectin (APN) levels decrease with age and obesity. On the other hand, a reduction in APN levels is associated with neurodegeneration and neuroinflammation. We previously showed that aged adiponectin knockout (APN-/-) mice developed Alzheimer's like pathologies, cerebral insulin resistance, and cognitive impairments. More recently, we also demonstrated that APN deficiency increased Aβ-induced microglia activation and neuroinflammatory responses in 5xFAD mice. There is compelling evidence that deregulated insulin activities or cerebral insulin resistance contributes to neuroinflammation and Alzheimer's disease (AD) pathogenesis. Here, we demonstrated that APN levels were reduced in the brain of AD patients and 5xFAD mice. We crossbred 5xFAD mice with APN-/- mice to generate APN-deficient 5xFAD (5xFAD;APN-/-). APN deficiency in 5xFAD mice accelerated amyloid loading, increased cerebral amyloid angiopathy, and reduced insulin-signaling activities. Pharmacokinetics study demonstrated adipoRon (APN receptor agonist) was a blood-brain barrier penetrant. AdipoRon improved neuronal insulin-signaling activities and insulin sensitivity in vitro and in vivo. Chronic adipoRon treatment improved spatial memory functions and ...Continue Reading

References

Oct 22, 2002·Journal of Neuropathology and Experimental Neurology·Mélanie CarpentierMieczyslaw Marcinkiewicz
Sep 5, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Andreas MarschnerChristian Büchel
Feb 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Robert M KoffieTara L Spires-Jones
Mar 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Shuko TakedaRyuichi Morishita
Aug 24, 2010·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·K UneH Arai
Feb 19, 2011·The International Journal of Neuropsychopharmacology·Chia-Hsiung ChenWeihong Song
Apr 15, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tao MaEric Klann
Jan 10, 2012·Cold Spring Harbor Perspectives in Medicine·Alberto Serrano-PozoBradley T Hyman
Feb 9, 2012·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Anjuli MishraStanley A Thayer
Mar 13, 2012·Metabolism: Clinical and Experimental·Takayuki MasakiHironobu Yoshimatsu
Jul 11, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jing LiuXin-Yun Lu
Oct 12, 2012·Neuromolecular Medicine·Antonio L TeixeiraOrestes V Forlenza
Dec 4, 2012·The Journal of Clinical Investigation·Philip T T LyWeihong Song
Jul 13, 2013·Frontiers in Aging Neuroscience·Kathleen R Zahs, Karen H Ashe
Nov 1, 2013·Nature·Miki Okada-IwabuTakashi Kadowaki
Nov 23, 2013·Nature Protocols·Marianne LegerThomas Freret
Oct 22, 2014·Proceedings of the National Academy of Sciences of the United States of America·Suk Yu YauKwok-Fai So
Jan 16, 2015·American Journal of Alzheimer's Disease and Other Dementias·Leung-Wing ChuJoyce Ha
May 15, 2015·Annals of Neurology·Michael T HenekaGabriele Doblhammer
Jul 29, 2015·Diabetes·Claudia A GrilloLawrence P Reagan
Jan 23, 2016·Journal of Diabetes and Its Complications·Natalia García-CasaresPedro González-Santos
Apr 16, 2016·Journal of Alzheimer's Disease : JAD·Masaaki WaragaiMakoto Hashimoto
Jun 25, 2016·Stroke; a Journal of Cerebral Circulation·Nevicia F CaseEric E Smith
Jul 20, 2016·The Journal of Experimental Medicine·Molly StanleyDavid M Holtzman
Dec 1, 2017·Frontiers in Cellular Neuroscience·Sarah NicolasAgnès Petit-Paitel
Aug 5, 2018·Molecular Neurobiology·Pedro CisternasNibaldo C Inestrosa

❮ Previous
Next ❯

Citations

Jul 16, 2020·Pharmaceuticals·Anishchal A Pratap, R M Damian Holsinger
Nov 22, 2020·Pharmaceuticals·Anishchal A Pratap, R M Damian Holsinger
Mar 7, 2021·International Journal of Molecular Sciences·Thomas H LeeSuk-Yu Yau
Apr 4, 2021·International Journal of Molecular Sciences·Jinsha LiuSepideh Afshar
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hubert ZatorskiJakub Fichna

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier & Cytokines

Some cytokines are able to cross the blood brain barrier through transport systems and enter the cerebrospinal fluid and interstitial fluid spaces. Here is the latest research on cytokines crossing the blood brain barrier and how this can affect tissues within the CNS.

Alzheimer's Disease: Microglia

Microglia are a type of glial cell found throughout the brain and spinal cord. Microglia have been found to be associated with Alzheimer's disease development and progression. Here are the latest discoveries pertaining to Alzheimer's disease and microglia.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.